一种新型光磁纳米探针的制备、表征及在体成像研究

发布时间：2018-01-17 20:20

本文关键词：一种新型光磁纳米探针的制备、表征及在体成像研究　出处：《西安电子科技大学》2015年硕士论文　论文类型：学位论文

【摘要】：近年来,越来越多的病患死于癌症,究其原因,主要是因为癌症早期发病不易被察觉,晚期发现又难以根治,癌症治疗对于目前医学界仍是一个巨大的挑战,所以在临床前以及临床中针对癌症的早期发现和治疗成为关键。目前医学界对于肿瘤的检测手段主要是使用传统的成像技术,如CT、超声成像、MRI和X线等,存在的问题是只有在器官发生明显病变后才能够被检测出。分子影像学的出现尤其是多模态成像技术不仅解决了传统影像学存在的问题,可以更早地的发现病变,而且多模态成像技术能够弥补单一成像模式存在的缺陷。多模态成像技术的核心问题是制备适用于多种成像模式的探针。针对该问题,本文制备出一种可以用于荧光成像和磁共振成像的双模态纳米探针。该光磁纳米探针的制备主要分为以下四步:(1)选择Cy5.5作为荧光标记物,使用NHS和EDC活化Cy5.5;(2)选择的磁性纳米颗粒为四氧化三铁,并使用CTAB将其改性为水溶性;(3)使用二氧化硅包覆四氧化三铁,表面吸附Cy5.5;(4)将PEI包覆在二氧化硅的最外层,使其与Mal-PEG-NHS中的的NHS反应。最终成功合成的光磁纳米探针表层裸露的基团为Mal,该基团可以为后期纳米探针交联抗体,制备具有主动靶向性的纳米探针提供可能,本实验最终制备的光磁纳米探针简记为CFN-NPs。为了验证该光磁纳米探针的理化性质以及其是否可被细胞吸收利用,本文进行以下实验验证:首先,体外表征证实其具有荧光信号和磁信号,粒径在纳米级别,分散性较好,可以被细胞和活体吸收;其次,细胞实验,验证了其具有较好的生物兼容性,较低的细胞毒性,可以被细胞顺利摄取;最后,活体荧光成像和磁共振成像实验证实了在活体中注射该光磁纳米探针,可以观察到明显的荧光信号和磁信号,并且该探针可以被动的靶向到肿瘤部位。通过实验证明,本文合成的光磁纳米探针具有条件要求温和,粒径均一,分散度较好并且稳定性好,可以被细胞内吞,活体实验荧光信号和磁信号明显,具有被动靶向肿瘤能力等特点,在将来有望用于临床前对肿瘤的检测。
[Abstract]:In recent years, more and more patients have died of cancer, mainly because the early onset of cancer is not easy to detect, the late detection is difficult to cure, cancer treatment is still a huge challenge to the medical profession. Therefore, the early detection and treatment of cancer before and in clinic becomes the key. At present, traditional imaging techniques, such as CTand ultrasound imaging, are mainly used in the detection of cancer in the medical field. The problem of MRI and X-ray is that it can only be detected when the organ changes obviously. The appearance of molecular imaging, especially the multi-mode imaging technology, not only solves the problems of traditional imaging. Lesions can be detected earlier, and multimodal imaging technology can make up for the shortcomings of a single imaging mode. The core problem of multi-mode imaging technology is to prepare probes suitable for multiple imaging modes. In this paper, a kind of bimodal nanoprobe which can be used in fluorescence imaging and magnetic resonance imaging is prepared. The preparation of the probe is divided into four steps: 1) choose Cy5.5 as fluorescent marker. Cy5.5 was activated by NHS and EDC. (2) the magnetic nanoparticles selected were Fe _ 2O _ 4 and modified to water solubility by CTAB. (3) Fe _ 2O _ 3 was coated with silica, and Cy5.5 was adsorbed on the surface. (4) PEI was coated on the outermost layer of silica to react with NHS in Mal-PEG-NHS. Finally, the surface exposed group of the photomagnetic nanoprobe was Mal. This group can be used to cross-link antibodies and prepare active targeting nanoprobes. In order to verify the physical and chemical properties of the probe and whether it can be absorbed by cells, the following experiments were carried out: firstly. In vitro characterization showed that it had fluorescence signal and magnetic signal. Its particle size was at the nanometer level and its dispersion was good. It could be absorbed by cells and living bodies. Secondly, the cell experiment proved that it has good biological compatibility, low cytotoxicity, and can be successfully ingested by cells. Finally, in vivo fluorescence imaging and magnetic resonance imaging experiments confirmed that in vivo injection of the optical magnetic nanoprobe, can be observed obvious fluorescence signal and magnetic signal. And the probe can be passively targeted to the tumor site. Through experiments, it is proved that the synthesized optomagnetic nanoprobe has mild conditions, uniform particle size, good dispersion and stability, and can be swallowed by cells. The fluorescence and magnetic signals of in vivo experiments are obvious and have the ability of passive targeting tumor, so it is expected to be used for the detection of tumor before clinical application in the future.
【学位授予单位】：西安电子科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R730.4;TB383.1

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